| Ye Yuan,Hu Han,Yu Jin,Xiao Zhou,Minxiao Yi,Yang Tang,Qianxia Li. Implications of the autophagy core gene variations on brain metastasis risk in non-small cell lung cancer treated with EGFR-TKI. Oncol Transl Med, 2020, 6: 185-192. |
| 自噬通路核心基因变异对EGFR-TKI治疗NSCLC脑转移发生风险的影响 |
| Implications of the autophagy core gene variations on brain metastasis risk in non-small cell lung cancer treated with EGFR-TKI |
| Received:June 25, 2020 Revised:October 09, 2020 |
| DOI：10.1007/s10330-020-0442-2 |
| 中文关键词: 自噬；非小细胞肺癌；脑转移；单核苷酸多态性；预测生物标志物 |
| 英文关键词: autophagy; non-small cell lung cancer (NSCLC); brain metastasis (BM); single nucleotide polymorphism; predictive biomarker |
| 基金项目:Supported by a grant from the National Natural Science Foundation of China (No. 81502521). |
| Author Name | Affiliation | E-mail | | Ye Yuan | Medical College, Shihezi University, Shihezi, Xinjiang, China | Shzuyuanye@Hotmail.com | | Hu Han | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Yu Jin | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Xiao Zhou | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Minxiao Yi | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Yang Tang | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Qianxia Li* | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | 49716393@qq.com |
|
| Hits: 9686 |
| Download times: 11119 |
| 中文摘要: |
| 目的：大脑是表皮生长因子受体（EGFR）突变的非小细胞肺癌患者治疗失败的主要部位。但是，很难识别哪些患者更容易发生脑转移（BM）。自噬对于癌症的发生和发展至关重要。我们假设自噬通路上核心基因的遗传变异可能会影响EGFR酪氨酸激酶抑制剂（EGFR-TKIs）治疗的非小细胞肺癌患者（NSCLC）的脑转移发生风险。
材料和方法：我们系统地检测了105位经TKI治疗的NSCLC患者中7个自噬核心基因的16个有潜在功能的单核苷酸多态性位点。通过绘制Kaplan-Meier曲线以评估累积脑转移发生概率。使用单因素和多因素Cox比例风险回归分析来计算风险比（HRs）和95％置信区间（CIs）。接下来，我们评估了这些基因变异与脑转移发生风险的潜在关联。
结果：我们发现ATG16L1：rs2241880，ATG10：rs10036653，rs3734114和ATG3：rs7652377这4个单核苷酸多态性与EGFR-TKIs治疗的NSCLC脑转移发生风险显著相关（所有P <0.05）。与rs7652377中AA基因型（12％），rs10036653中AT/TT基因型（16％），rs3734114中TT基因型（13％），或rs2241880中AG/GG基因型（17％）相比，ATG3:rs7652377 CC基因型（33％），ATG10:rs10036653 AA基因型（43％），ATG10：rs3734114 CT/CC基因型（46％）和ATG16L1:rs2241880 AA基因型患者的脑转移发生率更高（37％）。
结论：这些关联对于理解自噬在脑转移发生风险中的作用可能至关重要，因此需要进一步的前瞻性研究来确定对脑转移高风险患者进行预防性颅脑照射（PCI）是否可以得到生存获益。 |
| 英文摘要: |
| Objective The brain is the main site of failure in cancer patients with epidermal growth factor receptor
(EGFR) mutations undergoing treatment. However, identifying patients who may develop brain metastases
(BM) is difficult. Autophagy is critical for cancer initiation and progression. We hypothesized that genetic
variants in autophagy core genes might contribute to BM risk of non-small cell lung cancer (NSCLC)
following treatment with EGFR tyrosine kinase inhibitor (EGFR-TKIs).
Methods We systematically examined 16 potentially functional genetic polymorphisms in seven
autophagy core genes among 105 TKI-treated NSCLC patients. Kaplan-Meier curves were plotted to
assess the cumulative BM probability. Univariate and multivariate Cox proportional hazard regression
analyses were utilized to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We evaluated
the potential associations of these genes with subsequent BM development.
Results We found that ATG16L1: rs2241880, ATG10: rs10036653, rs3734114, and ATG3: rs7652377
are significantly associated with NSCLC treated with EGFR-TKIs (all P < 0.05). BM developed more often
in patients with ATG3 rs7652377 CC genotype (33%), ATG10 rs10036653 AA genotype (43%), ATG10:
rs3734114 CT/CC genotype (46%), and ATG16L1 rs2241880 AA genotype (37%) compared to patients with
AA genotypes at rs7652377 (12%), AT/TT genotypes at rs10036653 (16%), the TT genotype at rs3734114
(13%), or AG/GG genotypes at rs2241880 (17%).
Conclusion These associations may be critical for understanding the role of autophagy in BM risk.
Future prospective studies are needed to determine if prophylactic cranial irradiation (PCI) could offer a
survival benefit in this group of patients. |
|
View Full Text
Download reader HTML全文 |
| Close |
|
|
|